What is the Difference Between Interferon Beta 1A and 1B

The main difference between interferon beta-1a and 1b is that interferon-beta-1a is produced by mammal cells, but interferon-beta-1b is produced in modified E. coli. Therefore, interferon-beta-1a is glycosylated, while interferon-beta-1b is not. Consequently, interferon-beta-1a is the most immunogenic, while interferon-beta-1b is the least immunogenic. Furthermore, interferon-beta-1a reduces the frequency of flare-ups in patients with RRMS, while apart from RRMS, interferon-beta-1b is given for secondary progressive MS. Hence, interferon-beta-1a slows the progression of MS, while interferon-beta-1b delays in time to progression of MS. 

Interferon-beta-1a and 1b are two cytokines of the interferon family used to treat Multiple sclerosis (MS). In general, although interferons are not a cure for MS (there is no known cure); the claim is that interferons may slow the progress of the disease if it started early and continued for the duration of the disease.  

Key Areas Covered 

1. What is Interferon Beta 1A
      – Definition, Structure, Significance
2. What is Interferon Beta 1B
      – Definition, Structure, Significance
3. What are the Similarities Between Interferon Beta 1A and 1B
      – Outline of Common Features
4. What is the Difference Between Interferon Beta 1A and 1B
      – Comparison of Key Differences

Key Terms 

Cytokines, Immunogenic, Interferon Beta 1A, Interferon Beta 1B, Multiple Sclerosis (MS), RRMS (Relapsing-Remitting Multiple Sclerosis)

What is Interferon Beta 1A 

Interferon-beta-1a is one of the two types of interferon beta used in the treatment of MS. MS is a potentially disabling disease of the central nervous system, attacking the protective myelin sheath, which covers the nerve fibers. Therefore, it causes communication problems between the brain and the rest of the body. Interferon-beta-1a is, specifically useful for relapsing-remitting multiple sclerosis (RRMS). RRMS is the most common type of MS with relapses in patients of MS with periods of remission occurring in between. Here, interferon-beta-1a decreases the frequency of relapses.

Figure 1: Human Interferon Beta

Besides, interferon-beta-1a is one of the cytokines of the interferon family, showing the advance of disability in MS. Usually, it is produced in mammalian cells, from the natural human gene sequence and is glycosylated. Hence, it is the most immunogenic form of interferon beta. Moreover, Avonex interferon-1a and Rebif interferon-beta-1a are the commonly used forms of interferon beta-1a. Also, the manufacturer of the former is Biogen, France and the latter is Ares-Serono, UK. 

What is Interferon Beta 1B 

Interferon-beta-1b is the second type of interferon-beta important in treating MS. It is important for both RRMS and secondary progressive MS. Here, the secondary progressive MS is a stage of MS, occurring after RRMS, steadily worsening the disability. However, the use of interferon-beta-1b seems to decreases the frequency and the severity of relapses, delaying in time to progression of MS.

Figure 2: The Bruise Depicted Produced by Subcutaneous Injection

Moreover, interferon-beta-1b is produced by modified E.coli cells. Therefore, it does not undergo glycosylation, which is a post-translational modification only occurring in eukaryotic cells by selectively adding saccharides to a specific protein residue. Also, interferon beta-1b has a cysteine to serine substitution at position 17, deletion of the N-terminal methionine residue. Significantly, these two differences reduce the immunogenicity of interferon-beta-1b. 

Similarities Between Interferon Beta 1A and 1B 

• Interferon-beta-1a and 1b are two cytokines of the interferon family. 
• They are used in the treatment of MS to slow down the progression of the disease. 
• Usually, they produce about an 18–38% reduction in the rate of MS relapses.  
• Therefore, they are an established first-line treatment in relapsing-remitting MS.  
• Sometimes, antibodies generate in response to interferon beta administration. 
• However, the common side effects of interferon-beta include injection site reactions, flu-like symptoms, headache, muscle aches, nausea, diarrhea, etc. 

Difference Between Interferon Beta 1A and 1B 

Definition 

Interferon-beta-1a refers to the most immunogenic form of interferon beta produced by mammalian cells, while interferon-beta-1b refers to the least immunogenic form of interferon beta produced by E.coli. 

Interferon in the Market 

Avonex interferon-1a and Rebif interferon beta-1a are the two main forms of interferon beta-1a, while Betaferon/ Betaseron interferon-1b is the form of interferon beta-1b. 

Site of Production 

Interferon-beta-1a is produced in Chinese hamster ovary cells, while interferon-beta-1b is produced in E. coli bacteria cells.  

Amino Acid Sequence  

The amino acid sequence of interferon-beta-1a is identical to human interferon-beta, but the amino acid sequence of interferon beta-1b holds a Cysteine mutation at position 17.  

N-Terminal Methionine 

Interferon-beta-1a contains an N-terminal methionine, but interferon beta-1b has no N-terminal methionine. 

Glycosylation 

Interferon-beta-1a is glycosylated, but interferon beta-1b is not glycosylated. 

Molecular Weight 

The molecular weight of interferon beta-1a is 22–24 kDa, while the molecular weight of interferon beta-1b is 18.5 kDa. 

Immunogenicity 

Interferon-beta-1a is 10-times more immunogenic, but interferon beta-1b is the least immunogenic form of interferon beta. 

Therapeutic Use 

Interferon-beta-1a is important in treating RRMS, while interferon beta-1b is important for both RRMS and secondary progressive MS. 

Therapeutic Effect 

Interferon-beta-1a mainly decreases the frequency of relapses while interferon beta-1b decreases both frequency and the severity of relapses. 

Consequences 

Interferon-beta-1a slows the progression of disability, while interferon beta-1b delays in time to progression of MS. 

Specific Activity 

The specific activity of interferon-beta-1a is >300 MIU/mg while the specific activity of interferon-beta-1b is 32 MIU/mg.  

Route of Administration 

Avonex interferon-1a is administrated through intramuscular (IM) only while Rebif interferon beta-1a is administrated through subcutaneous (SC) only. Meanwhile, Betaferon/ Betaseron interferon-1b is administrated through subcutaneous (SC) only. 

Side Effects 

The common side effects of interferon-beta-1a include headache (67%), flu-like symptoms (61%), myalgia (34%), etc. Meanwhile, the common side effects of interferon-beta-1b include injection site reaction (85%), headache (84%), flu-like symptoms (76%), fever (59%), etc. 

Conclusion 

Interferon-beta-1a is the type of interferon-beta produced in mammalian cells. Therefore, it undergoes glycosylation. Also, it is the most immunogenic form of interferon beta. It is mainly important for treating in RRMS, decreasing the frequency of relapses of MS. Meanwhile, interferon beta-1b is the second type of interferon-beta produced by E. coli cells. Hence, it does not undergo glycosylation and it is 10 times less immunogenic than interferon-beta-1a. Interferon beta-1b is important in treating both RRMS and secondary progressive MS. Usually, it delays in time to progression of MS. Thereby, the main difference between interferon beta-1a and 1b is the structure, immunogenicity, and administration. 

References:

1. Giovannoni, G. “Neutralising Antibodies to Interferon Beta during the Treatment of Multiple Sclerosis.” Journal of Neurology, Neurosurgery & Psychiatry, vol. 73, no. 5, Jan. 2002, pp. 465–469., doi:10.1136/jnnp.73.5.465.

Image Courtesy:

1. “1AU1 Human Interferon-Beta01” By Nevit Dilmen (CC BY-SA 3.0) via Commons Wikimedia  
2. “Implant” By Alison Cassidy – Own work (CC BY-SA 3.0) via Commons Wikimedia